The objective of this project is to define the regulation of contractile protein activity in brain and specifically as they relate to release and uptake of neurotransmitters by synaptosomal enriched fractions. Regulatory brain proteins respond to calcium in a fashion similar to regulatory protein of muscle. In brain, however, they are separated. Myosin on synaptic vesicles binds actin complex on synaptosomal membranes and their association apparently permits contractile effects on synaptic vesicles with release of neurotransmitters. As in muscle, such brain synaptosomal activity is apparently complemented by alpha-actinin, a new protein recently reported by us to be present in brain. It appears to exist in extractable amounts from synaptosomal fractions particularly associated with synaptic vesicles. This localization has added new emphasis to the concept that components of the contractile system are vital to synaptic vesicle functions. We propose to study further the properties of alpha-actinin(as an additional part of the complex of relaxing or modulatory proteins by determining their biochemical activity, localizing these proteins within the synaptosomal structures by preparing ferritin-conjugated antisera against each of these proteins, and finally to determine their involvement in the mechanism that produces uptake and release of neurotransmitters in brain. Attempts will be made to correlate structure and function of brain contractile proteins with clinical findings in neurological disorders.